Recent achievements and future developments in advanced and recurrent cervical cancer: trials of the Gynecologic...

Following publication of five pivotal randomized trials of concurrent chemo-irradiation for patients with locally advanced cervical cancer (ie, International Federation of Gynecology and Oncology (FIGO] stages IB2-IVA) in 1999 and 2000, the National Cancer Institute issued a Clinical Alert advising that concurrent chemotherapy (typically, single-agent cisplatin) be incorporated into the treatment program of women scheduled to receive definitive pelvic radiotherapy. Although the adoption of this new standard has improved overall survival and decreased the recurrence rate by 50%, for those patients who do relapse, the prognosis is very poor and, ultimately, therapy in this setting is palliative in nature. The Gynecologic Oncology Group (GOG) has now completed eight randomized trials for metastatic and recurrent cervical cancer, all of which have studied cisplatin-based regimens. The eighth trial (protocol 204) compared four cisplatin-based doublets containing paclitaxel, topotecan, vinorelbine, or gemcitabine. Because the vast majority of patients are now expected to receive cisplatin "up front" as part of primary therapy with pelvic radiation, there are concerns for the development of drug-resistant clones in recurrences both inside and outside of the radiation field. The GOG has recently reported the results from a phase II trial evaluating the anti-vascular agent, bevacizumab, in women who were eligible for second-line or third-line therapy for metastatic and/or recurrent disease (protocol 227C). It becomes imperative that we continue to evaluate novel regimens for this disease.